Measles virus （MV） is highly contagious pathogen, which causes a profound immunosuppression, resulting in high infant mortality. This virus infects dendritic cells （DCs） following the binding of MV hemagglutinin ...Measles virus （MV） is highly contagious pathogen, which causes a profound immunosuppression, resulting in high infant mortality. This virus infects dendritic cells （DCs） following the binding of MV hemagglutinin （MV-H） to CD150 receptor and alters DC functions by a mechanism that is not completely understood. We have analyzed the effect of MV-H interaction with CD150-expressing DCs on the DC signaling pathways and consequent phenotypic and functional changes in the absence of infectious context. We demonstrated that contact between CD150 on human DCs and MV-H expressed on membrane of transfected CHO cells was sufficient to modulate the activity of two major regulatory pathways of DC differentiation and function： to stimulate Akt and inhibit p38 MAPK phosphorylation, without concomitant ERK1/2 activation. Furthermore, interaction with MV-H decreased the expression level of DC activation markers CD80, CD83, CD86, and HLA-DR and strongly downregulated IL-12 production but did not modulate IL-IO secretion. Moreover, contact with MV-H suppressed DC-mediated T-cell alloproliferation, demonstrating profound alteration of DC maturation and functions. Finally, engagement of CD150 by MV-H in mice transgenic for human CD150 decreased inflammatory responses, showing the immunosuppressive effect of CD150-MV-H interaction in vivo. Altogether, these results uncover novel mechanism of MV-induced immunosuppression, implicating modulation of cell signaling pathways following MV-H interaction with CD150-expressing DCs and reveal anti-inflammatory effects of CD150 stimulation.展开更多
In this article,published online on 15 June 2015,there was an unintended error during the image processing of Figs.2 and 4.In Fig.2c,the time point 12 h was omitted and is included in the corrected Fig.2c.Figure 4a an...In this article,published online on 15 June 2015,there was an unintended error during the image processing of Figs.2 and 4.In Fig.2c,the time point 12 h was omitted and is included in the corrected Fig.2c.Figure 4a and b contain blots not intended for that experiment,which now have been replaced with the blots generated for that experiment.The conclusions drawn from the presented experiments remain unaltered,and this correction has no bearing on the final outcome of the study.The inconvenience caused by this error is deeply regretted.展开更多
文摘Measles virus （MV） is highly contagious pathogen, which causes a profound immunosuppression, resulting in high infant mortality. This virus infects dendritic cells （DCs） following the binding of MV hemagglutinin （MV-H） to CD150 receptor and alters DC functions by a mechanism that is not completely understood. We have analyzed the effect of MV-H interaction with CD150-expressing DCs on the DC signaling pathways and consequent phenotypic and functional changes in the absence of infectious context. We demonstrated that contact between CD150 on human DCs and MV-H expressed on membrane of transfected CHO cells was sufficient to modulate the activity of two major regulatory pathways of DC differentiation and function： to stimulate Akt and inhibit p38 MAPK phosphorylation, without concomitant ERK1/2 activation. Furthermore, interaction with MV-H decreased the expression level of DC activation markers CD80, CD83, CD86, and HLA-DR and strongly downregulated IL-12 production but did not modulate IL-IO secretion. Moreover, contact with MV-H suppressed DC-mediated T-cell alloproliferation, demonstrating profound alteration of DC maturation and functions. Finally, engagement of CD150 by MV-H in mice transgenic for human CD150 decreased inflammatory responses, showing the immunosuppressive effect of CD150-MV-H interaction in vivo. Altogether, these results uncover novel mechanism of MV-induced immunosuppression, implicating modulation of cell signaling pathways following MV-H interaction with CD150-expressing DCs and reveal anti-inflammatory effects of CD150 stimulation.
文摘In this article,published online on 15 June 2015,there was an unintended error during the image processing of Figs.2 and 4.In Fig.2c,the time point 12 h was omitted and is included in the corrected Fig.2c.Figure 4a and b contain blots not intended for that experiment,which now have been replaced with the blots generated for that experiment.The conclusions drawn from the presented experiments remain unaltered,and this correction has no bearing on the final outcome of the study.The inconvenience caused by this error is deeply regretted.
